Mark Gudesblatt, MD

The Epidemiologyof Progressive MultifocalLeukoencephalopathyJohn F. Foley, MDRocky Mountain Multiple SclerosisClinic, Salt Lake City, Utah.IntroductionProgressive multifocal leukoencephalopathy (PML)is a rare disease that is generated by a change in therelationship between the human host and residentJC virus (JCV). Prior to the epidemic of acquiredimmunodeficiency syndrome (AIDS), fewer than250 cases had been reported worldwide. 1 Otherthan AIDS, in which 3% to 5% of individuals developPML, 2 this disease has been an unusual complicationof myeloproliferative or lymphoproliferativedisorders and immunosuppressant therapiesadministered to control autoimmune diseases ormalignancies. 3 However, the now well-documentedpotential for treatment-related PML that hasoccurred during use of the novel biologically activeselective therapeutics has intensified efforts toidentify the molecular steps as well as the risk factorsthat permit the transition from benign (archetypal)JCV infection to neurotrophic JCV infectionof the central nervous system (CNS). In addition toJCV seropositivity, at least two other factors appearto define risk. These are altered immune functionand extended exposure to the immunomodulatingagent. Detailed epidemiology of PML may be usefulto the effort to isolate factors that render individualssusceptible to PML. It may also aid calculationsof the risk of PML in relation to expected benefitsfrom immunomodulating agents.Dr. Foley has received consulting fees from Biogen Idec,Genzyme, and Teva and has received honoraria fromBiogen Idec and Teva.JCV and PML: History andEarly Epidemiology StudiesPML, first described in the late 1950s in threepatients with hematologic malignancies, is a demyelinatingdisorder of the white matter characterizedby lytic infection of cells in the CNS, par-S10 July 2011 • Clinical Reviews of JCV and PML